[4+3]-Cycloaddition/Quasi-Favorskii Processes

本项目的重点是探索[4+3]-环加成/准Favorskii过程。该反应序列，它提供了快速访问高度复杂的结构，将被应用于三种天然产物的合成：前列腺素类三环克拉维酮，生物碱麦哲伦和抗结核药物elisapterosin B。每一种天然产物将允许一个独特的环状烯丙基阳离子的[4+3]-环加成的发展，从环戊烯基到环庚烯基。两种不同的协议产生的烯丙基阳离子将进行研究。环加合物的准Favorskii重排将是总合成努力的一个组成部分。该反应将提供原则上可以直接通过二烯与环烯基甲醛的Diels-Alder环加成获得的化合物。环加成过程之间的立体化学差异表明，[4+3]-环加成将更适合于目标的全合成。互补的环加成过程将比较计算和实验的情况下，与环戊二烯和其他环状二烯的环加成。非环状二烯的分子间和分子内[4+3]-环加成/准Favorskii过程也将被探索。有了这个奖项，有机和大分子化学计划支持哥伦比亚的密苏里州大学化学系的Michael Harmata教授的研究。Harmata教授和他的学生正在开发一种快速构建复杂有机分子结构的不寻常而有效的途径。正在探索的方法，结合成环的“环加成”反应与随后的分子重排反应，将被应用到几个天然存在的分子的合成，以建立其通用性和普遍性。总体思路是利用独特的工艺结合简单的起始材料，快速增加分子的复杂性。复杂的有机结构通常在新药或新材料的开发中发挥关键作用，随着分子医学和纳米技术的发展，这些新材料将变得越来越重要。

This project is focused on the exploration of a [4+3]-cycloaddition/quasi-Favorskii process. This reaction sequence, which provides rapid access to highly complex structures, will be applied to the synthesis of three natural products: the prostanoid tricycloclavulone, the alkaloid magellaninone and the antitubercular agent elisapterosin B. Each natural product will allow the development of the [4+3]-cycloaddition of a unique cyclic allylic cation, from cyclopentenyl to cycloheptenyl. Two different protocols for generating the allylic cations will be studied. The quasi-Favorskii rearrangement of the cycloadducts will be an integral part of the total synthesis efforts. This reaction will afford compounds that could in principle be obtained directly through the Diels-Alder cycloaddition of dienes with cycloalkenyl carboxaldehydes. Stereochemical differences between the cycloaddition processes suggest that the [4+3]-cycloaddition will be more suited for the total syntheses of the targets. The complementary cycloaddition processes will be compared both computationally and experimentally in the context of cycloadditions with cyclopentadiene and other cyclic dienes. Intermolecular and intramolecular [4+3]-cycloaddition/quasi-Favorskii processes of noncyclic dienes will also be explored.With this award, the Organic and Macromolecular Chemistry Program is supporting the research of Professor Michael Harmata, of the Department of Chemistry at the University of Missouri at Columbia. Professor Harmata and his students are developing an unusual and efficient route for the rapid construction of complex organic molecular structures. The methodology under exploration, combining a ring-forming "cycloaddition" reaction with a subsequent molecular rearrangement reaction, will be applied to the synthesis of several naturally occurring molecules in order to establish its versatility and generality. The general idea is to take advantage of unique processes combined with simple starting materials to increase molecular complexity quickly. Complex organic structures often play critical roles in the development of new drugs or new materials that will be increasingly important as technological developments in molecular medicine and nanotechnology increase.